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Published on: October 21, 2017
Dualistic evolution of liver damage in mice triggered by a single sublethal exposure to Microcystin-LR
L J Mattos1, S S Valença2, S M F O Azevedo1
1Laboratory of Ecophysiology and Toxicology of Cyanobacteria, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Microcystins (MCYST) are the most frequently reported cyanotoxins in human poisoning incidents. Despite the well-described mechanism of acute and lethal injury, the sublethal effects of this toxin require further investigation. The aim of this study was to contribute to the knowledge of the variant MCYST-LR effects at sublethal doses by investigating biochemical changes and tissue damage in a murine model. For this purpose, mice were intraperitoneally injected with 45 μg of MCYST-LR/kg body weight. Their organs were collected at 2, 8, 24, 48 or 96 h after injection. Control animals received saline solution. We detected oxidative imbalance in the liver, particularly at 8 h after exposure. Furthermore, biomarkers of liver injury were detected in high concentration in the serum of the exposed animals. Stereological analyses of the liver indicated two different phases in the intoxication process: an initial phase characterized by an increase in steatosis was followed by a second, later phase characterized by increased inflammation and hepatocyte binucleation. Formation of areas of necrosis and increased blood vessel diameter were observed throughout the experimental period. The number of hepatocytes per area unit also decreased. However, these parameters recovered over the period of exposure. MCYST accumulated in liver and was detectable until the end of the monitoring period. These results confirm the necessity for further studies of processes involved in sublethal exposure to MCYST.
Insights
Sublethal doses of microcystins (MCYST) cause liver damage, including oxidative stress and inflammation, in mice. While some damage recovers, MCYST accumulates in the liver, necessitating further research into long-term effects.
Area of Science:
- Environmental toxicology
- Hepatotoxicity
- Cyanotoxin research
Background:
- Microcystins (MCYST) are prevalent cyanotoxins linked to human poisoning.
- Sublethal effects of MCYST require further investigation beyond acute toxicity.
Purpose of the Study:
- To investigate the biochemical and tissue damage effects of sublethal doses of MCYST-LR in a murine model.
- To elucidate the temporal progression of MCYST-LR intoxication at the cellular and organ levels.
Main Methods:
- Mice were injected with MCYST-LR (45 μg/kg) and organs collected at various time points (2–96 h).
- Biochemical markers of liver injury and oxidative stress were analyzed.
- Stereological analyses assessed liver tissue damage, including steatosis, inflammation, necrosis, and hepatocyte changes.
Main Results:
- Oxidative imbalance and elevated liver injury biomarkers were observed in exposed mice.
- Two distinct phases of liver intoxication were identified: initial steatosis followed by inflammation and hepatocyte binucleation.
- Necrosis and increased blood vessel diameter occurred, with partial recovery of hepatocyte numbers, while MCYST persisted in the liver.
Conclusions:
- Sublethal MCYST-LR exposure induces significant, biphasic liver damage characterized by oxidative stress and inflammation.
- MCYST accumulation in the liver suggests potential for chronic toxicity.
- Further research is crucial to understand the mechanisms underlying sublethal microcystin exposure and its long-term health implications.
